Proteins and nucleic acids employ only a small fraction of the functionality available to the modern chemist yet solve with ease chemical problems in binding, specificity, and catalysis that are well beyond the reach of current rational chemical design. These biopolymers can be diversified to generate numerous variants from which molecules with desired properties can be selected by Nature or by researchers in the laboratory. The sequence space of a 50 residue protein includes 1065 variants, while that of a 50 base oligonucleotide contains 1030 molecules.
In vitro molecular evolution efforts include diversification of a starting molecule into related variants from which desired molecules are chosen. Methods used to generate diversity in nucleic acid and protein libraries include whole genome mutagenesis (E. A. Hart et al. Journal of the American Chemical Society 1999, 121, 9887-9888.), random cassette mutagenesis (J. F. Reidhaar-Olson et al. Methods Enzymol 1991, 208, 564-86), error-prone PCR (R. C. Caldwell and G. F. Joyce. PCR Methods Applic. 1992, 2, 28-33), and DNA shuffling (Stemmer. Nature 1994, 370, 389-391). After diversification, biopolymers can be selected with novel or enhanced properties.